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Asthma is a chronic, episodic disease of the airways. In 1997, the National Heart, Lung, and Blood Institute in the United States included the following features as integral to the definition of asthma;    (i) recurrent episodes of respiratory symptoms;    (ii) variable airflow obstruction that is often reversible, either spontaneously or with treatment;    (iii) presence of airway hyperresponsiveness and    (iv) chronic airway inflammation in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells.
All of these features need not be present in any given asthmatic patient. Although the absolute “minimum criteria” to establish a diagnosis of asthma is not widely agreed upon, the presence of airway hyperresponsiveness is a common finding in patients with current symptoms and active asthma.
Clinicians have long known that asthma is not a single disease. Rather, it exists in several forms. This heterogeneity has been established by a variety of studies which have indicated disease risk from early environmental factors and susceptibility genes; and subsequent disease induction and progression from inflammation as well as response to therapeutic agents. Asthma is an inflammatory disease and is not simply due to excessive smooth muscle contraction. Asthma is a chronic disease of the airways, however it is unknown whether inflammation initiates asthma or whether asthma initiates inflammation. In the lungs of healthy individuals inflammation is a common occurrence, and is in fact necessary to maintain normal lung homeostasis through the removal of pathogens such as bacteria and viruses and pollutants which are present in the air. In the lungs of an asthmatic, an exaggerated response occurs in response to irritants which results in an increased tendency to produce excessive airway narrowing (hyperresponsiveness). Increased airway inflammation follows exposure to inducers such as allergens, viruses, exercise, or non-specific irritant inhalation. Increased inflammation leads to exacerbations characterized by dyspnea, wheezing, cough, and chest tightness. Abnormal histopathologic lesions including oedema, epithelial cell desquamation, and inflammatory cell infiltration are found not only in severe asthma cases but even in patients with very mild asthma.
Asthma is therefore a disease in which inflammation of the airways causes airflow obstruction. When an asthma attack occurs, the muscles of the bronchial tree become tight and the lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound. Mucus production is increased. Most people with asthma exhibit periodic wheezing attacks separated by symptom-free periods. Some asthmatics exhibit chronic shortness of breath with episodes of increased shortness of breath. Other asthmatics may exhibit coughing as their predominant symptom. Asthma attacks can last minutes to days, and can become dangerous if the airflow becomes severely restricted.
In sensitive individuals, asthma symptoms can be triggered by inhaled allergens (allergy triggers), such as pet dander, dust mites, cockroach allergens, molds, or pollens. Asthma symptoms can also be triggered by respiratory infections, exercise, cold air, tobacco smoke and other pollutants, stress, food, or drug allergies. Aspirin and other non-steroidal anti-inflammatory medications provoke asthma in some patients.
Asthma is the Western world's most widespread chronic health problem. In Australia alone, it affects over 2 million Australians:                1 in 4 children        1 in 7 teenagers        1 in 10 adults.        
Asthma treatment is aimed at avoiding known allergens and respiratory irritants and controlling symptoms and airway inflammation through medication. In terms of medication, there are two basic classes of medication for the treatment of asthma:    (i) Long term control medications—used on a regular basis to prevent attacks, not for treatment during an attack:            inhaled steroids (e.g. triamcinolone acetonide, beclomethasone, flunisolide, fluticasone propionate, and budesonide) prevent inflammation        leukotriene inhibitors (e.g. montelukast sodium, zafirlukast)        long-acting bronchodilators (e.g. formoterol, salmeterol) help keep airways open        cromolyn sodium or nedocromil sodium        theophylline        combination of corticosteroid and bronchodilator, using either separate inhalers or a single inhaler (e.g. fluticasone/salmeterol and budesonide/formoterol).        anti-IgE therapy (e.g. omalizumab).            (ii) Quick relief (rescue) medications—used to relieve symptoms during an attack:            short-acting bronchodilators (e.g. salbutamol, fenoterol, terbutaline, and albuterol) aminophylline            (iii) In addition, oral or intravenous corticosteroids (e.g. prednisone, methylprednisolone) are used to stabilize severe episodes.
Nevertheless, despite significant progress in terms of understanding the cellular basis of asthma and the development of a range of treatment options, the cause of asthma is not known, nor has there been a cure developed. Accordingly, there is an ongoing need to pursue asthma-related research at the level of both understanding its cause and developing new treatment regimens which can contribute to expanding the existing range of therapeutic and prophylactic treatments which are available to the public.
To this end, one aspect of asthma etiology which remains relatively poorly understood is the occurrence of airway tissue remodelling. The natural history of airway remodelling is poorly understood and although it occurs in many patients with asthma, it is not always a universal finding. Pathologically, airway remodelling appears to have a variety of features that include an increase in smooth muscle mass, mucus gland hyperplasia, persistence of chronic inflammatory cellular infiltrates, release of fibrogenic growth factors along with collagen deposition. Many biopsy studies show these pathological features from the airways of patients with chronic asthma. However, there are many unanswered questions, including whether features of remodelling are related to an inexorable progression of acute or chronic airway inflammation or whether remodelling is a phenomenon separate from inflammation altogether.
Lymphangioleiomyomatosis (LAM) is a rare lung disease that affects only females, usually in their thirties, and for which the prognosis is generally extremely poor. Until recently, it was thought that survival rates post-diagnosis were about 10 yrs, but this has been revised and current estimates are closer to 15 yrs. Although the pathogenesis remains unclear, an association with tuberous sclerosis (TSC) is largely accepted (39% of TSC patients have LAM); however, this is not universal. The LAM cell is thought to be a form of smooth muscle that is abnormally proliferative and underlies the formation of characteristic LAM nodules in the lung and angiolipomas in the kidney. The pulmonary nodules are responsible for cystic destruction of the lung, recurrent pneumothoraces and a steady decline in pulmonary function. There is some debate as to whether the abnormal smooth muscle cell arises in the airway or the vasculature and some have suggested that it may be a result of a distant metastasis. The LAM smooth muscle cell is heterogeneous and LAM cells may differ in their degree of differentiation. Ultimately the hyperproliferation of LAM cells in the lungs of affected individuals leads to a reduction in the transfer of oxygen and will result in respiratory failure. Current treatment options have been ineffective in reversing disease progression, and for many affected individuals lung transplantation is used as the last resort.
Accordingly, there remains a need for effective therapeutic and prophylactic options for the treatment of diseases and conditions associated with airway tissue remodelling, such as asthma and LAM.